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Curcumin의 전처리는 excitotoxin에 의한 세포사멸로부터 해마신경세포를 보호

Pretreatment of curcumin protects hippocampal neurons against excitotoxin-induced cell death

  • 김소정 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원) ;
  • 김근호 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원) ;
  • 공경혜 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원) ;
  • 이재원 (부산대학교 약학대학 약학과, 신약개발연구소, 장수생명과학기술연구원)
  • Kim, So-Jung (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Kim, Keun-Ho (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Kong, Kyoung-Hye (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University) ;
  • Lee, Jae-Won (Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University)
  • 발행 : 2007.01.29

초록

Curcumin은 자연에 존재하는 황색의 페놀성분의 커리 향신료이며 항산화 및 항염증의 성질을 가지고 있어서 산화 스트레스와 면역염증과 관련한 여러 질병의 치료로 사용되어져 왔다. 이러한 curcumin의 항산화 및 항염증 효과는 여러 퇴행성 신경질환으로부터 뇌를 보호하는데 유용하게 적용될 수 있다. 본 연구에서는 glutamate에 의한 excitotoxicity로부터 해마신경세포를 보호하는 curcumin의 신경보호효과에 대하여 보고한다. 태아 생쥐의 해마로부터 얻어진 신경세포를 저농도의 curcumin으로 전처리한 경우, 신경세포는 glutamate에 의한 세포사멸로부터 보호되었다. 그러나 이러한 신경보호효과는 산화스트레스의 조절과는 무관하였다. 흥미롭게도 고농도의 curcumin전처리는 오히려 초대배양 신경세포의 세포사멸을 유도하였다. 해마신경세포에서 스트레스 반응 단백질인 HSP70이 저농도의 curcumin을 처리하였을 때 현저하게 증가하였으며 반면 세포사멸의 마커인 절단된 PARP의 양은 고농도의 curcumin을 처리하였을 때 급증함이 immunoblot분석을 통하여 관찰되었다. 이러한 발견은 curcumin이 excitotoxin인 glutamate에 대한 신경세포의 반응을 조절할 수 있음을 보여주고 curcumin과 관련 화합물들의 퇴행성 신경질환에서의 예방 및 치료법으로의 가능성을 제시하고 있다.

Curcumin is a natural phenolic yellow curry spice, derived from the tumeric, which has been used for the treatment of diseases associated with oxidative stress and inflammation. Curcumin is known to have both anti-oxidative and anti-inflammatory properties. These properties can be beneficial to protect the brain from the neurodegenerative diseases. We now report the neuroprotective effects of curcumin pretreatment in primary hippocampal neurons to glutamate-induced excitotoxicity. Pretreatment of embryonic mouse hippocampal cell cultures with low does of curcumin protected neurons against glutamate-induced death, however, this neuroprotection was not correlated with the modulation of oxidative stress. Interestingly, high dose of curcumin showed the cytotoxicity in primary cultured hippocampal neurons. Immunoblot analyses showed that levels of stress response. protein HSP70 were significantly elevated in neurons exposed to low dose of curcumin, whereas levels of cleaved PARP were increased in neurons exposed to high dose of curcumin. These findings show that curcumin can modulate neuronal responses to glutamate, and suggest possible use of curcumin and related compounds in the prevention and/or treatment of neurodegenerative disorders.

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